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ARDS = acute respiratory distress syndrome; ATC = automatic tube compensation; Ccw - chest wall compliance; Cl = lung compliance; COPD = chronic obstructive pulmonary disease; CPAP = con

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ARDS = acute respiratory distress syndrome; ATC = automatic tube compensation; Ccw - chest wall compliance; Cl = lung compliance; COPD = chronic obstructive pulmonary disease; CPAP = continuous positive airway pressure; Crs = respiratory system compliance; IPL = inspiratory pres-sure level; LIP = lower inflection point; MIP = maximal inspiratory prespres-sure; NIPPV = noninvasive positive prespres-sure ventilation; Pavg = average inspira-tory pressure; Paw = airway pressure; PEEP = positive end expirainspira-tory pressure; PEFR = peak expirainspira-tory flow rate; Pes = esophageal pressure; Pex = end-expiratory pressure; Ps = inspiratory pressure; PTI = pressure time index; PTP = pressure time product; PV = pressure–volume curve; RSBI = rapid shallow breathing index; SBT = spontaneous breathing trial; UIP = upper inflection point; Vt = tidal volume; WOB = work of breathing

Abstract

Pulmonary disease changes the physiology of the lungs, which

manifests as changes in respiratory mechanics Therefore,

measure-ment of respiratory mechanics allows a clinician to monitor closely

the course of pulmonary disease Here we review the principles of

respiratory mechanics and their clinical applications These

principles include compliance, elastance, resistance, impedance,

flow, and work of breathing We discuss these principles in normal

conditions and in disease states As the severity of pulmonary

disease increases, mechanical ventilation can become necessary

We discuss the use of pressure–volume curves in assisting with

poorly compliant lungs while on mechanical ventilation In addition,

we discuss physiologic parameters that assist with ventilator

weaning as the disease process abates

Introduction

In humans ventilation involves movement of the chest wall to

produce a pressure gradient that will permit flow and movement

of gas This can be accomplished by the respiratory muscles, by

negative pressure ventilation (iron lung), or by positive pressure

ventilation (mechanical ventilator) Measurements of respiratory

mechanics allow a clinician to monitor closely the course of

pulmonary disease At the bedside, changes in these mechanics

can occur abruptly (and prompt immediate action) or they may

reveal slow trends in respiratory condition (and prompt initiation

or discontinuation of mechanical ventilation) Here we focus on

the mechanical measurements that can be used to help make

clinical decisions

Compliance

In respiratory physiology, lung compliance describes the

willingness of the lungs to distend, and elastance the

willing-ness to return to the resting position Compliance is

deter-mined by the following equation: C =∆V/∆P, where C is compliance, ∆V is change in volume, and ∆P is change in pressure The inverse of compliance is elastance (E ~ 1/C) Airway pressure during inflation is influenced by volume, thoracic (lung and chest wall) compliance, and thoracic resistance to flow Resistance to flow must be eliminated if compliance is to be measured accurately This is accomplished by measuring pressure and volume during a period of zero flow, termed static measurements Therefore, compliance is determined by taking static measurements of the distending pressure at different lung volumes and can be done during inflation or deflation [1] Plotting pressure measurements throughout the respiratory cycle allows a pressure–volume (PV) curve to be constructed (Fig 1) The slope of this curve is equal to the compliance The inspiratory and expiratory curves are separated on the PV curve; this area of separation is termed hysteresis Hysteresis develops in elastic structures when the volume change from

an applied force is sustained for some time after the force is removed [2] In the lungs, hysteresis results both from the collapse of small airways and from the surface tension at the gas–liquid interface of alveoli that must be overcome to inflate the lungs The degree of hysteresis is greater when a breath is initiated near the residual volume and less when it is initiated at higher lung volumes [2] Both the chest wall and the lung influence respiratory compliance The total thoracic compliance is less than individual compliances of the chest or lung because the two add in parallel (elastances, the inverse, add in series) [3]: Crs = Ccw × Cl/(Ccw + Cl), where Crs, Ccw, and Cl are the compliances of the respiratory system, chest wall, and lung, respectively (Fig 2 and Table 1)

Review

Clinical review: Respiratory mechanics in spontaneous and

assisted ventilation

Daniel C Grinnan1 and Jonathon Dean Truwit2

1Fellow, Department of Pulmonary and Critical Care, University of Virginia Health System, Virginia, USA

2E Cato Drash Professor of Medicine, Senior Associate Dean for Clinical Affairs, Chief, Department of Pulmonary and Critical Care, University of Virginia Health System, Virginia, USA

Corresponding author: Daniel C Grinnan, dg6j@virginia.edu

Published online: 18 April 2005 Critical Care 2005, 9:472-484 (DOI 10.1186/cc3516)

This article is online at http://ccforum.com/content/9/5/472

© 2005 BioMed Central Ltd

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Reduced compliance can be caused by a stiff chest wall or

lungs, or both The distinction can be clinically significant To

separate the contribution made by each to total lung

compliance, a measure of intrapleural pressure is needed

The most accurate surrogate marker for intrapleural pressure

is esophageal pressure, which can be measured by placing

an esophageal balloon [1] However, this is rarely done in

clinical practice Alternatively, changes in central venous

pressure can approximate changes in esophageal pressure,

but this technique is yet to be verified [1]

Respiratory system compliance is routinely recorded at the bedside of critically ill patients In mechanically ventilated patients, this is done by measuring end-expiratory alveolar pressure (Pex) and end-inspiratory alveolar pressure (also called peak static or plateau pressure [Ps]), so that the change in volume is the tidal volume (Vt) Alveolar pressure can easily be assessed after occlusion of the airway, because the pressure in the airway equilibrates with alveolar pressure Pex is the pressure associated with alveolar distention at the end of a breath In normal individuals this is usually zero when

Figure 1

Pressure–volume curve Shown is a pressure–volume curve developed from

measurements in isolated lung during inflation (inspiration) and deflation

(expiration) The slope of each curve is the compliance The difference in the

curves is hysteresis Reprinted from [3] with permission from Elsevier

Figure 2

Compliance of the lungs, chest wall, and the combined lung–chest wall system At the functional residual capacity, the forces of expansion and collapse are in equilibrium Reprinted from [3] with permission from Elsevier

Table 1

Causes of decreased intrathoracic compliance

Causes of decreased measured chest wall compliance Causes of decreased measured lung compliance

Neuromuscular weakness (Guillain–Barre, steroid myopathy, etc.) Dynamic hyperinflation

Cryptogenic organizing pneumonitis Lymphangitic spread of tumor Shown are the causes of decreased intrathoracic compliance, partitioned into causes of decreased measured chest wall compliance and causes of decreased measured lung compliance

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referenced to atmosphere However, when positive

end-expiratory pressure (PEEP) is applied, Pex is at least as great

as PEEP It may be greater if air trapping occurs, and the

associated pressure beyond PEEP is termed auto-PEEP or

intrinsic PEEP The clinician will need to know Ps, Pex,

auto-PEEP, and Vt to determine respiratory compliance at the

bedside For example, if the PEEP is 5 cmH2O, auto-PEEP is

0 cmH2O, Ps is 25 cmH2O, and Vt is 0.5 l, then Crs = ∆V/∆P

= 0.5 l/(25 – 5) = 0.5/20 = 0.025 l/cmH2O or 25 ml/cmH2O

In a normal subject on mechanical ventilation, compliance

should be greater than 50–100 ml/cmH2O [4]

Patients with obstructive lung disease have a prolonged

expiratory phase At baseline, most patients with emphysema

have increased compliance (because of decreased elastance

of the lungs) If the Vt is not completely exhaled, then a

certain amount of air will be ‘trapped’ in the alveoli If this

continues over several breaths, then it will result in ‘stacking’

of breaths until a new end-expiratory thoracic volume is

achieved As the volume increases (dynamic hyperinflation),

the functional residual capacity will be increased As a result,

tidal breathing will occur at a less compliant portion of the PV

curve (Fig 3)

The pressure difference associated with the trapped volume

is called auto-PEEP Caution must be used in a patient who

has obstructive lung disease and is on mechanical ventilation

Usually, such patients are treated aggressively for airway

inflammation (bronchodilator treatments and corticosteroids),

while the respiratory rate is decreased and the expiratory

phase of respiration is prolonged If the functional residual

capacity is increased, delivering the same Vt may increase

the transalveolar pressure, which can impede venous return

(resulting in hypotension) or lead to a pneumothorax The

development of hypotension in a patient with dynamic

hyperinflation should prompt the clinician to listen to the

lungs and assess the ventilator for auto-PEEP If auto-PEEP is

suspected, then the patient should be disconnected from the

ventilator to determine whether the hypotension resolves when delivered breaths are withheld (Fig 4)

Auto-PEEP can be measured in patients on mechanical ventilators by creating an expiratory pause The end-expiratory pause maneuver allows the pressure transducer of the ventilator to approximate the end-expiratory alveolar pressure, or auto-PEEP Some ventilators allow the clinician

to create and control the expiratory pause, whereas other ventilators perform an end-expiratory pause as an automated function that requires only the push of a button Measure-ments of auto-PEEP require a passive patient because patient interaction in breathing will alter the measurements of the pressure transducer In the intensive care unit, this usually requires sedation and, occasionally, paralysis

Decreasing the amount of auto-PEEP on mechanical ventilation requires one to decrease the respiratory rate and prolong the expiratory phase of ventilation Execution of these goals often requires eliminating patient effort through heavy sedation or paralysis Once patient effort is eliminated, it is important to follow respiratory mechanics closely, including auto-PEEP and compliance In order to protect the lungs from barotrauma, it is common to permit a certain amount of hypoventilation, termed permissive hypercapnia Permissive hypercapnia has been proven safe and allows a clinician to use the lowest respiratory rate and Vt possible, thus protecting the lungs while they are impaired

Patients with auto-PEEP (or intrinsic PEEP) who require mechanical ventilation are often asynchronous with the ventilator During assisted modes of ventilation, patients with auto-PEEP often have difficulty triggering the ventilator to initiate a breath The patient must first overcome the auto-PEEP before creating the negative intrapleural pressure required to trigger the ventilator The patient can be assisted

by applying extrinsic PEEP, of a magnitude less than Pex, to the circuit Now the pressure needed to be generated by the

Figure 3

Compliance in emphysema and fibrosis Shown are changes in the compliance of the inspiratory limb of the pressure–volume curve with respect to

(a) chest wall, (b) lungs, and (c) combined lung-chest wall system in patients with emphysema and fibrosis The functional residual capacity (FRC),

represented on the vertical axis at a transmural pressure of 0, is elevated in emphysema, which can lead to dynamic hyperinflation Reprinted from [3] with permission from Elsevier

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patient to trigger the ventilator is decreased because the

trigger sensitivity of the ventilator is centered around the

applied extrinsic PEEP and not atmospheric pressure

Therefore, more patient initiated efforts will be able to trigger

the ventilator successfully

Acute respiratory distress syndrome (ARDS) is a common

condition in the intensive care unit and is characterized by low

compliance Typically, the start of inspiration occurs at low

volumes (near the residual volume) and requires high pressure

to overcome surface tension and inflate the alveoli The

relation between pressure and surface tension is explained by

Laplace’s Law, which relates pressure to radius in spherical

structures: P = 2T/r, where P = pressure, T = surface tension,

and r = radius Below we discuss the role of PV curves in

patients with ARDS who require mechanical ventilation

Pressure–volume curves and ventilator

management in ARDS

The PV curve of the lung and chest wall is obtained by

plotting the corresponding pressure at different Vts As

mentioned previously, the resulting slope is the compliance of

the lung and chest wall In recent years, much interest has

centered on using the PV curve to help select the optimal

ventilator settings for patients on mechanical ventilation

Patients with ARDS on mechanical ventilation have been the

focus of this attention

There are various ways to measure the PV curve in patients

on mechanical ventilation Each method has advantages and

disadvantages [5] Some methods require specialized

equipment that is not available in all intensive care units With

the syringe technique, the patient is removed from the

mechanical ventilator and a 2 l syringe is placed on the

endo-tracheal tube Increments of 50–150 cc of 100% oxygen are delivered, and a transducer measures the corresponding airway pressure at each volume [2] These values are then plotted and connected to form the PV curve An alternative approach is to use the multiple occlusion technique With this method, the patient remains on the ventilator The plateau pressure is measured at different Vts (ranging from 200 cc to

1300 cc) and plotted to form the PV curve It is important to allow several breaths at a standard volume between measurements to obtain the most accurate result A recent study [5] showed that the multiple occlusion technique and the syringe technique yield similar measurements A third approach is the continuous low-flow technique Maintaining a low inspiratory flow rate on the mechanical ventilator (less than 10 l/min) minimizes resistance, permitting estimation of the PV curve [2] All methods used to obtain a PV curve generally require a passive patient for accurate results The risks associated with sedation and paralysis (which may be needed) should be considered before proceeding to create a

PV curve

The PV curve will change with time and with differences in pressure [5] In ARDS, the PV curve will change as the disease progresses or resolves [6] In the early (exudative) stage, the PV curve generally exhibits low compliance and a well demarcated lower inflection point (LIP) As the disease progresses (fibrotic stage), the compliance remains low but the LIP is obscured [2] ARDS is also associated with a rapidly changing clinical course The shape of a PV curve may change over several hours in the same patient Therefore, up-to-date measurements are needed before ventilator settings are manipulated, if one is relying upon the PV curve Traditionally, the PV curve has been calculated with zero end-expiratory pressure [7-9] When calculated with different levels of PEEP, the PV curve will be altered [8,9] In addition, the ventilator mode and level of ventilation that a patient is on before calculation of a PV curve can affect the shape of the curve [9] These drawbacks make it difficult to know whether

PV curves may be relied upon for bedside use (Fig 5)

The inspiratory phase of the PV curve consists of three sections The first section occurs at a low volume, and is nonlinear and relatively flat (low compliance) As the volume increases, the second section of the curve is linear and has a steeper slope (higher compliance) The third section of the curve is again nonlinear and flat (return to low compliance) The junction between the first and second portion of the curve is called the LIP The LIP can be calculated by inter-secting the lines from the first and second portions of the curve Alternatively, the LIP can be calculated by measuring the steepest point of the second section and then marking the LIP as the point of a 20% decrease in slope from this steepest point Studies assessing interobserver reliability have varied Some have found good interobserver variability, whereas others have found significant variability [2,5,7] The junction of the second and third portions of the curve is

Figure 4

Ventilator tracing with a square wave, or constant flow, pattern Note

that the machine is triggered to initiate a breath before flow returns to

zero (the horizontal axis) This indicates that auto-PEEP (positive

end-expiratory pressure) is present and directs the clinician to investigate

further

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called the upper inflection point (UIP) The UIP can be

measured in the same way as the LIP (except the UIP would

represent a 20% increase from the point of the greatest

slope) Studies have generally found that there is good

interobserver agreement and good agreement between

methods for measuring UIP [5,10]

The LIP and UIP are points that represent changes in

compliance In the past, the LIP was thought to represent the

end of alveolar recruitment The opening of an alveolus during

inspiration was thought to cause shear stress that would be

harmful to the lung Therefore, by setting the amount of PEEP

above the LIP, the level of shear stress could be decreased

[11,12] The UIP was thought to represent the start of

alveolar overdistension It was thought that if the airway

pressure exceeded the UIP, then harmful alveolar stretch and

overdistension would occur [11,12] In keeping the level of

PEEP above the LIP and the plateau pressure below the UIP,

the patient would receive Vts at the most compliant part of

the PV curve By following the PV curve over time, the

ventilator settings could be individually tailored to provide the

maximal benefit and the minimal damage to the patient with

ARDS requiring mechanical ventilation

In 1999, Amato and coworkers [11] reported the results of a

prospective, randomized, controlled trial using the PV curve

as a guide to ventilation The level of PEEP was maintained at

2 cmH2O above the LIP in the experimental group, with a

plateau pressure of 20 cmH2O or less When compared with

‘conventional ventilation’ (use of lower PEEP, higher Vts, and

higher plateau pressures), there was a significant difference

in mortality at 28 days (38% versus 71%) and a significant

difference in the rate of weaning favoring the experimental

group This study supported the clinical practice of setting the PEEP at 2 cmH2O above the LIP However, because the plateau pressure was also manipulated, it is difficult to attribute the mortality difference to PEEP Moreover, the mortality rate in the control group was higher than expected, because other studies conducted in ARDS patients have consistently found mortality rates around 40% in control arms [13]

It is now apparent that alveoli are recruited throughout the inspiratory limb of the PV curve (not just below the LIP, as was previously assumed) [14,15] We now believe that the LIP represents a level of airway pressure that leads to increased recruitment of alveoli This increased recruitment is sustained throughout the second portion of the PV curve and

is reflected by a steep slope, indicating increased compliance The UIP, in turn, represents a point of decreased alveolar recruitment Recruitment of alveoli on inspiration begins in the nondependent portion of the lungs and slowly spreads to the dependent portion of the lungs [16] Areas of atelectasis may require inspiratory pressures above

40 cmH2O before alveoli will be recruited [16] Clearly, in this model of the PV curve, setting the PEEP above the LIP will not reduce shear stress by starting inspiration after alveolar recruitment

The model of continuous recruitment also dissociates the LIP from PEEP [16] Previously, when the LIP was thought to represent the completion of alveolar recruitment, the PEEP that corresponded to the LIP was thought to sustain alveolar recruitment and prevent alveolar shear stress However, because alveoli are continually recruited along the inspiratory limb of the PV curve, the ‘optimal PEEP’ may be difficult to determine from the inspiratory limb Moreover, PEEP is an expiratory phenomenon, and it corresponds to pressures on the expiratory curve rather than the inspiratory curve [17] Because hysteresis exists between the inspiratory and expiratory limbs, it is difficult to estimate the effect that PEEP will have on the inspiratory curve [17,18]

Clinical studies attempting to improve outcomes in ARDS by varying levels of PEEP have had disappointing results In

2004 the ARDS Network investigators [19] reported a prospective study comparing the effects of lower PEEP (mean 8–9 cmH2O) with those of higher PEEP (mean 13–15 cmH2O) The results did not reveal a significant difference in clinical outcomes (mortality, time of ICU stay, time on mechanical ventilator) between the two groups In that study, the LIP was not used to guide the ‘high PEEP’ group as had been done in the study conducted by Amato and coworkers A weakness of the study was that the level of PEEP used in the ‘high PEEP’ group was changed during the study, potentially altering the outcome [20]

Clinical research has proven that large Vts are detrimental in ARDS In 2000, findings were reported by the ARDS Network investigators [21] In that prospective, randomized,

Figure 5

The inspiratory limb of the pressure–volume curve (dark line) divided

into three sections Section 1 (low compliance) and section 2 (high

compliance) are separated by the lower inflection point (LIP) Section

2 (high compliance) and section 3 (low compliance) are separated by

the upper inflection point (UIP) In this example, the LIP is marked at

the point of crossing of the greatest slope in section 2 and the lowest

slope of section 1 The UIP is marked at the point of 20% decrease

from the greatest slope of section 2 (a calculated value)

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controlled trial, low Vts (yielding plateau pressures

< 30 cmH2O) were compared with higher Vts (plateau

pressures up to 50 cmH2O) The results showed a significant

decrease in mortality (from 37% to 31%) when the lung

protective strategy (low Vt of 6 ml/kg predicted body weight)

was used That study did not use PEEP as part of the

ventilator strategy for lung protection However, the

assumption is that, by limiting Vt, fewer patients will reach a

plateau pressure greater than the UIP Therefore, alveolar

overdistension and excessive stretch will be minimized

Intuitively, one might assume that the largest benefit would be

in the subset of patients with the poorest compliance

However, the mortality difference was independent of

respiratory system compliance, leading the investigators to

attribute the benefit to other factors (such as stretch)

However, it is not clear that the UIP can be used to set plateau

pressure and therefore avoid harmful alveolar stretch It has

been shown that alterations in alveolar recruitment will change

the UIP [14,22] This supports the idea that the UIP represents

a decrease in alveolar recruitment Therefore, the UIP would

not be expected to predict reliably an alveolar phenomena

unrelated to recruitment (such as stretch or overdistension)

At present, we do not recommend routine use of the inspiratory

PV curve in patients with ARDS Measurements can be time

consuming and, as evident from the above discussion,

meaningful interpretation is difficult Instead of setting PEEP

values just above the LIP, we currently recommend following

the nomogram used by the ARDS Network [21] Recently,

more attention has been given to the expiratory limb of the PV

curve As mentioned above, PEEP is an expiratory

measurement, and the appropriate setting of PEEP may be

estimated by a point on the expiratory curve Holzapfel and

coworkers [23] recently showed that, when manipulating PEEP

according to the inflection point on the deflation limb of the PV

curve, intrapulmonary shunting was maximally reduced (when

compared with the LIP) Although further studies are needed to

define the role of the expiratory curve in ARDS, the rationale

and small clinical trials appear promising

Flow and resistance

Flow (Q) is the movement of air Flow is dependent on a

pressure gradient (∆P) and is inversely related to the resistance

to flow (R) This relationship is described in the following

equation: Q = ∆P/R In the lungs, two types of flow are present

– laminar flow and turbulent flow In general, turbulent flow is

present in large airways and major bifurcations, whereas

laminar flow is present in the more distant airways The type of

flow present in an airway is influenced by the rate of flow (V),

the airway radius (r), the density of gas (p), and the viscosity of

gas (η) Reynold’s number is a calculation of the above

variables used to determine whether flow will be turbulent or

laminar Reynold’s number = 2Vrp/η, and values greater than

2300 generally indicate that flow will have a turbulent

component Flow with a Reynold’s number greater than 4000

is completely turbulent [24]

In airways governed by laminar flow, resistance is related to the radius (r), airway length (l), and gas viscosity (η) through Poiseuille’s Law (R = 8ηl/πr4) This equation highlights the strong relation of the radius on resistance (i.e doubling the radius decreases the resistance 16-fold) When flow is turbulent (in large airways), the equation for flow must also incorporate a frictional factor (f) The modification of Poiseuille’s equation for turbulent flow is as follows: R = Vflη/π2r5[25]

At each division of the airways, the branches of the lungs lie

in parallel With resistances in parallel, the total resistance (Rt) is less than the individual resistances (1/Rt = 1/R1 + 1/R2 + 1/R3 + …) Because of their large number and parallel arrangement, the bronchioles are not the primary site of greatest resistance In a spontaneous breathing, normal person, the medium-sized bronchi are the site of greatest resistance [3] The flow–volume loop demonstrates airflow at different points in the respiratory cycle A normal flow–volume loop is shown in Fig 6

In a normal individual maximal inspiratory flow is limited only

by muscle strength and total lung and chest wall compliance Resistance to flow is minimal and does not limit inspiration Maximal expiratory flow is initially limited only by expiratory muscle strength (when the airway radius is large and resistance is minimal) However, as the airway lumen decreases, resistance to flow will increase and flow is limited

by resistance The accurate measurement of airway resistance during spontaneous breathing requires placement

of an esophageal balloon to estimate pleural pressure [1] This allows for the determination of the pressure gradient (transpulmonary pressure equals pleural minus airway pressure) at any given lung volume Through extrapolating flows at the same volume from a flow–volume loop, an isovolume flow–pressure curve can be established (Fig 7)

By manipulating the pressure gradient at different lung volumes (through increasing pleural pressure), it has been shown that maximal flow is limited once a volume-specific pleural pressure is achieved Several physiologic theories have been put forward in an attempt to explain this expiratory flow limitation [26]

The wave speed theory of flow limitation is derived from fluid mechanics When airflow approaches the speed of wave propagation within the airway wall, flow will be limited According to this model, the cross-sectional area of the airway, the compliance of the airway, and the resistance upstream from the flow limiting segment all contribute to flow limitation This theory has been well validated during expiration, when vital capacity is between 0% and 75% of the total lung capacity [26] At a vital capacity greater than 75%

of total lung capacity, it has been difficult to limit flow by increasing pleural pressure in normal individuals [27] Therefore, traditional teaching indicated that early expiration

is primarily limited by effort dependent muscle strength [27]

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However, a recent model in normal individuals showed that

peak expiratory flow was limited by mechanical properties of

the lung (in accordance with the wave speed mechanism),

and not by muscle strength [26] As peak flow normally

occurs at around 80% of total lung capacity, the wave speed

theory can be used to explain expiratory flow limitation from a

vital capacity of 80% and less [26]

Patients with asthma and chronic bronchitis have airway

inflammation, which decreases the radius of the airway By

decreasing the radius, the resistance to flow is increased (in

accordance with Poiseuille’s Law) This is most prominent

during expiration, when the increase in resistance leads to

decreased flow and ‘air trapping’ The peak expiratory flow

rate (PEFR) is a common bedside measure of expiratory flow

in patients with asthma With good patient effort, limitations in

PEFR are likely caused by the mechanical properties of the

airways (such as decreased cross-sectional area) Assuming

that a patient is able to generate a similar pressure gradient

on subsequent measures of PEFR, differences in flow would

reflect differences in airway resistance, and differences in

airway resistance correlate with inflammation and disease

severity In fact, peak flow has correlated well with airway

hyperresponsiveness, and diurnal variation in peak flows

correlate well with diurnal variation in symptoms [28] In

addition, peak flow levels of less than 100 l/min have been

associated with need for hospitalization and oral steroid

therapy [29] PEFR is frequently used at home by asthmatic

persons in order to provide an objective measure of disease

activity [30,31]

Heliox is a combination of helium and oxygen, and is available

as 60%, 70%, or 80% helium The decreased density of

helium can decrease the total density of the gas by 300%

(with 80% helium) Because airway resistance is directly

influenced by density (Poiseuille’s Law), there has been much

interest in using heliox to reduce resistance during acute

exacerbations of asthma Unfortunately, a recent

meta-analysis conducted by the Cochrane Airway Group [32]

failed to find significant benefit from the existing studies Observational data and case reports suggest that heliox assists patients with vocal cord dysfunction, a disorder characterized by increased resistance to expiratory flow at the level of the vocal cords It may also be useful with other types of upper airway obstruction

Inspiratory resistance can easily be approximated in patients requiring mechanical ventilation The pressure gradient for flow is constant throughout a constant flow breath Once this pressure gradient is established, inspiratory resistance can

be measured at any point in the respiratory cycle, provided the airway pressure and the pressure distending the alveoli and chest wall are known The pressure gradient that drives flow is easily determined near the end of inspiration, subtracting end-inspiratory plateau pressure (peak static or plateau pressure) from peak airway pressure (peak dynamic pressure) Therefore, inspiratory resistance equals peak dynamic pressure minus plateau pressure, divided by flow (Ri = [Pd – Ps]/V) In a normal individual inspiratory resis-tance rarely exceeds 15 cmH2O/l per s [4] In mechanically ventilated patients, a sudden increase in peak pressures without an increase in plateau pressure signifies a sudden increase in resistance A cause for the increased resistance should immediately be sought, because the most common causes (problem with ventilator circuit, mucous in the airway,

or bronchospasm) can be readily treated

The size of the endotracheal tube can be critical in deter-mining the cause of elevated resistance [25] Because flow in

Figure 6

Flow–volume loop A flow–volume loop is shown, with exhalation

above the horizontal axis and inspiration below

Figure 7

The maximal flow–volume curve The isovolume flow–pressure curve (left) is created from measurements of pleural pressure and expiratory flow at different volumes of forced expiration These measurements can

be extrapolated to show a maximal flow–volume curve (right) Note that, at a volume specific pleural pressure, the maximal expiratory flow will be limited VC, vital capacity Reprinted from [1] with permission from Elsevier

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the trachea is turbulent, the resistance is inversely

propor-tional to the radius of the trachea to the fifth power Because

most endotracheal tubes are significantly smaller than the

trachea, resistance to flow is significantly increased [25] To

maintain flow, the pressure gradient must be appropriately

increased With traditional modes of weaning from mechanical

ventilation (pressure support), a level of pressure support is

maintained to overcome the resistance in the endotracheal tube

Automatic tube compensation (ATC) is a method of reducing

the work needed to overcome the increased resistance of the

endotracheal tube [33] ATC is a flow triggered mode that

varies pressure levels throughout the respiratory cycle Studies

have found that the increased work of breathing caused by

high endotracheal tube resistance is decreased with ATC

when compared with pressure support [33,34]

Least squares fit method

As described above, traditional methods for measuring

respiratory mechanics require ventilator manipulation

Maneuvers such as inspiratory pause, expiratory pause, and

airway occlusion have been used to measure variables such

as compliance, resistance, and auto-PEEP More advanced

ventilators have built-in pressure transducers and

pneumo-tachographs to permit continuous measurement of pressure

and flow By incorporating these data into mathematical

models, such as the least squares fit method, measurements

of respiratory mechanics can potentially be monitored

continuously and without ventilator manipulation Through

constant knowledge of flow, pressure, and volume (obtained

through the integration of flow), other variables (compliance,

resistance, and auto-PEEP) can be resolved

Small series have compared the least squares fit method with

traditional methods, and have tielded promising findings The

least squares fit method correlates well with traditional

methods of measuring compliance, resistance, and

auto-PEEP [35,36], but it is not in widespread use at present The

technology for computing continuous measurements and

computing by the least squares fit method is not readily

available in most intensive care units A potential weakness of

the least squares fit method is that data are presented for a

block of time, usually a single breath If the start of inspiration

or the end of exhalation are not measured correctly by the

ventilator, the measurements will be incorrect [36] Although

this does not present a major problem in paralyzed patients,

interaction between patient and ventilator can skew the

mechanical measurements Also, the mathematics of ‘fitting’

nonlinear patient breaths into linear mathematical models will

always create some degree of error At this time the least

squares fit method of calculating respiratory mechanics is

intriguing, and further work will help to define its role in the

intensive care unit

Work of breathing and impedance

Impedance to airflow includes the resistance to airflow as

well as the force required to overcome the elasticity of the

lungs and chest wall The inertia of the airway is also part of impedance, but its contribution is negligible in respiratory physiology Impedance can be estimated through measure-ments of the work of breathing (WOB)

Work is defined as the product of pressure and volume (W =

P × V) In respiratory physiology, WOB describes the energy required as flow begins to perform the task of ventilation The calculation of WOB is usually associated with inspiratory effort, because expiration is generally a passive process However, in patients with air trapping or acute respiratory failure, expiration can be an active process and can require significant work As the WOB increases, increased demand

is imposed on the respiratory muscles The respiratory muscles of patients in acute respiratory distress will use an increasing percentage of the cardiac output (which can induce ischemia in patients with coronary artery disease) As the demand increases, the respiratory muscles will eventually fatigue Bellemare and Grassino [37] first described the diaphragmatic threshold for fatigue as the product of inspiratory time and the change in transdiaphragmatic pressure with inspiration When the diaphragmatic threshold for fatigue exceeded 0.15, the task of ventilation could not be performed for longer than 45 min As the diaphragm fatigues, the accessory muscles of respiration are recruited, and the respiratory rate is increased When fatigue leads to inadequate ventilation, carbon dioxide levels in the blood increase and indicate a need for mechanical ventilation

Usually, the goal of mechanical ventilation is to provide the vital organs with adequate oxygenation and ventilation while decreasing the WOB As the underlying disease process resolves, the ventilator work is decreased and the patient’s WOB is increased until the patient is able to approximate the WOB needed when extubated From the above discussion, it should be apparent that estimating the WOB in patients breathing spontaneously and on mechanical ventilation can

be clinically important WOB can be determined through analysis of a PV plot, where work is the area under the curve Therefore, integrating the PV plot yields WOB In such a plot, pressure represents the sum of the transpulmonary pressure gradient and the chest wall pressure gradient

In a spontaneously breathing patient, transpulmonary pressure can be measured by placing an esophageal balloon, because esophageal pressure (Pes) estimates pleural pressure However, there is no direct method for measuring the chest wall pressure gradient Three estimates of the chest wall gradient have been used to assess the WOB indirectly [1] First, the chest wall gradient can be estimated using computer analysis The equation of motion (P = V/C + [Q × R])

is the basis of computer analysis for pulmonary mechanics [38] When modified for the chest wall, resistive forces (Q × R) can be eliminated, and the equation describes the elastic forces of the chest wall (Pcw = Vt/2Ccw) or work (product of average inflation pressure and Vt): W = Vt2/2Ccw [1]

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Second, the chest wall pressure gradient can be estimated

by delivering a known volume to a passive patient and

measuring the change in esophageal pressure By adding

this pressure to that of a spontaneous breath of the same

volume and integrating the area, The WOB can be estimated

(Fig 8) In a patient receiving mechanical ventilation, the

WOB can be measured directly In a passive individual

(resulting from heavy sedation or paralysis), the WOB can be

determined by measuring the average inspiratory pressure

(Pavg) and multiplying it by the volume Several methods of

determining average inspiratory pressure can be used

During spontaneous breathing or while the patient is

receiving mechanically delivered breaths, the equation of

motion can be modified to determine the Pavg: Pavg =

(Vt/ti × R) + (Vt/2C) + Pex, where ti = inspiratory time In this

modification, Pex is the end-expiratory pressure Therefore,

Pavg will indicate the pressure needed to overcome frictional

forces, elastic forces, and impedance, as well as the pressure

resulting from hyperinflation

During mechanical ventilation in a passive patient, Pavg and

WOB can be determined by integrating the airway pressure

(Paw)–volume plot, with Pavg determined by dividing the

area by Vt Alternatively, airway pressure at mid-inspiratory

time or mid-volume can be used to estimate Pavg This is the

easiest method, but it is not the most accurate, and during

constant flow inflation the Paw–time tracing can be used to

determine Pavg This tracing can be obtained at the bedside

by transducing Paw using a hemodynamic pressure monitor

[1] Finally, Pavg can be determined from commonly recorded

airway pressures – peak inspiratory pressure (Pd), Ps, and

Pex – during constant flow inflation In this case, Pavg = Pd –

(Ps – Pex)/2 (Fig 9) [1]

In most circumstances, the mechanically ventilated patient

will perform part of the WOB, while the ventilator will provide

the remainder To estimate the WOB done by the patient,

measurements must be taken when the patient is active

(participating in ventilation) and when they are passive (the

ventilator does all of the work while the patient is heavily

sedated or paralyzed) During volume modes of ventilation,

the Paw–volume plot can be integrated to estimate the work

By measuring the difference in the WOB between

patient-active and patient-passive breaths, the patient’s WOB on a

volume assist mode can be determined Alternatively, an

esophageal balloon can be placed to measure pleural

pressure accurately After a Pes–volume plot is constructed,

the difference between active and passive breaths can

determine patient’s WOB Although esophageal balloon

placement yields more accurate results, it is rarely done in

clinical practice

Determination of the WOB in patients on pressure modes of

ventilation is more complicated [1] If the patient is passive,

measurements can be made as explained above However, if

the patient is participating in the WOB (pressure support mode), the initial effort produces a negative transthoracic pressure (pleural pressure) When the machine is triggered, positive pressure is applied and the transthoracic pressure increases Therefore, the change in pressure from a PV plot

on the ventilator will not accurately reflect the total change in pressure The airway pressure from the ventilator can be used

to estimate muscular effort and calculate the WOB, but this

is difficult Alternatively, an esophageal balloon can be placed and the integral of Pes and flow can be used to calculate the lung’s WOB The equation of motion must then be used to estimate the work performed by the chest wall, and the thoracic WOB can then be determined

In different individuals with the same WOB, the respiratory efficiency (WOB/oxygen consumption of respiratory muscles) can have wide variation [39] This variation can be understood by noting that the calculation of work requires a change in volume In respiratory physiology, energy can be expended during the isometric phase of respiration The pressure time product (PTP) is the product of the average inspiratory pressure (starting from the onset of effort) and the duration of inspiration: PTP = Pavg × Ti The PTP was developed to account for energy expenditures during the dynamic and isometric phases of respiration Therefore, the PTP will more directly measure the total energy (in addition to the total work) of breathing [1,39]

Traditionally, the PTP has been measured as the time integral

of the difference between the esophageal pressure tracing and the recoil pressure of the chest wall [40] However, this

Figure 8

Calculating the work of breathing during spontaneous ventilation using

an esophageal balloon Area A represents the work to move air into and out of the lungs Area B represents the work to expand the chest wall and is calculated from a pressure–volume curve in a passive patient receiving a mechanically generated breath The sum of A and B represents the total work of breathing, and it can be determined through integration of the product of esophageal pressure and flow Reprinted from [1] with permission from Elsevier

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method may not account for energy expenditure needed to

overcome the load on inspiratory muscles at the beginning of

inspiration in patients with dynamic hyperinflation [40] The

traditional measurement may also fail to account for the

energy needed to stop active expiration [40] Determination

of ‘upper bound PTP’ and ‘lower bound PTP’ have enabled

calculations of PTP throughout the respiratory cycle so that

total energy expenditure can be approximated (Fig 10)

The pressure time index (PTI) expands on the PTP It is

deter-mined by the following equation [1,41]: PTI = (Pavg/MIP) ×

(Ti/Ttot), where MIP is the maximal inspiratory pressure that

can be generated by an individual, Ti is the duration of

inspiration, and Ttot is the duration of the respiratory cycle

By including the measurements used in the PTP, the PTI also

yields a more reliable estimate (compared with WOB) of the

total energy expended in respiration Addition of the MIP to

the calculation of PTI permits determination of the respiratory

effort as related to respiratory strength MIP can easily be

calculated at the bedside of a mechanically ventilated patient

with the use of a one-way valve [1] Inclusion of the Ttot in the

PTI permits the duration of energy expenditure in the

respiratory cycle to be compared with the duration of rest

The PTI, much like the diaphragmatic threshold for fatigue of

Bellemare and Grassino [37], has been used to predict the

likelihood of subsequent respiratory fatigue and the need for

intubation [41,42] Conversely, it has been applied to

prediction of successful discontinuance of mechanical

ventilation in patients weaning from mechanical ventilation

[43,44] A weakness of the PTI in determining success of

extubation is that it does not incorporate the respiratory rate

A common reaction of patients in respiratory failure is to

increase the respiratory rate and to decrease Vt in order to

decrease the subjective sensation of dyspnea In such

patients, the PTI would decrease as the Vt decreased

Quantifications of the inspiratory WOB have also been

applied to prediction of weaning success Unfortunately,

these calculations, like the PTI, have not proven to be highly predictive, limiting their use at the bedside Other measures that are simpler to determine have proven to be more useful and are discussed in the following part of the review

Discontinuation of mechanical ventilation

As stated above, successful discontinuation of mechanical ventilation will depend on close assessment of the patient’s respiratory mechanics while on the ventilator In addition to assessing the mechanics, there are many other considerations First, it is important to recall the indication for mechanical ventilation and intubation Some indications (e.g altered mental status, upper gastrointestinal bleed threatening airway safety, inability to handle secretions, recurrent aspiration, hemoptysis) may be accompanied by normal respiratory mechanics, but mechanical ventilation may

be necessary until the indication for intubation has been addressed For example, a patient with severe alteration in mental status requiring intubation for airway protection should have improved mental status, require suctioning less than every 2 hours, be able to follow basic commands, and have a cough and gag reflex before extubation However, in patients intubated for respiratory failure, assessment of respiratory mechanics before extubation can help to predict the success

of extubation

Weaning trials are recommended for patients with prolonged intubation or cardiopulmonary causes for intubation [45] In general, a weaning trial involves reducing the work performed

by the ventilator while monitoring for evidence of fatigue or altered gas exchange There are several different ways to perform a weaning trial Pressure support ventilation is a mode of ventilation characterized by patient triggered ventilation with both an inspiratory pressure level (IPL) and PEEP The IPL and PEEP are gradually decreased to minimal levels before extubation Although exceptions occur, the IPL should usually be less than 12 cmH2O and the PEEP should

be less than 7 cmH O before extubation is attempted

Figure 9

Calculation of work per liter of ventilation (Pavg) in a passive patient on constant-flow mechanical ventilation Pavg can be calculated by three

methods (a) Dividing the integral of the airway pressure (Paw) by the inspiratory time (Ti) (b) Recording the airway pressure at the mid-inspiratory time (Ti/2) (c) Calculating Pd – (Ps – Pex)/2, where Pd = peak inspiratory pressure, Ps = estimate of end-inspiratory pressure, and Pex = estimate

of end-expiratory pressure Reprinted from [1] with permission from Elsevier

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